Highly efficient synthesis of DNA binding polyamides for commercial exploitation

Gene transcription is a central biological process that occurs in every living cell. It involves reading the genetic information stored in the cell's DNA and converting this into RNA. The ability to artificially regulate this process is a highly sought after goal in biotechnology and medicine as it would offer a tool that could validate new drug targets, investigate new biology as well as providing new therapeutics. DNA binding polyamides are small molecules that can regulate gene transcription. They are the only class of small molecules that can target virtually any DNA sequence, yet a significant barrier to widespread adoption is the ability to manufacture diverse collections of polyamides in high yield and purity in a quick cost-effective manner. A novel method for the synthesis of DNA-binding polyamides has been developed at Leicester that enables their preparation in high yield and purity and at low cost; thus overcoming the major barrier to market entry. The Leicester method results in increases in overall yield of up to 330-fold relative to the current state of the art.The aim of this Follow-on Fund project is to automate and optimise the scalable production of polyamides and to further biological validation by end users and licensees. These pre-commercialisation activities will enhance the patented technology for commercialisation and lay the foundation for their widespread utilisation in biology and medicine.

Social and Economic Impact We have highlighted three sectors in which we feel the impact will be strongly felt. * Biotechnology (Timeframe 2-5 years) - Technologies that can regulate gene expression are in high demand with the projected global market for the gene silencing method known as RNA interference (RNAi) alone approaching $3.6 billion by 2013. Since polyamides address several of the shortfalls of RNAi and have proven efficacy in vivo, we predict that access to these molecules would provide a competitive gene silencing product vying for a share in this market. * Healthcare devices (Timeframe 2-5 years) - We envisage that this technology will enable the integration of polyamides into the next generation of point of care diagnostic devices. The point of care (POC) diagnostic market is growing at over 11 % with a global market share worth $11.3 billion in 2007. * Therapeutics (Timeframe 5-10 years) - Polyamides have known therapeutic potential for the treatment of a wide range of diseases including cancer and in cardiovascular disease. Cancer and cardiovascular disease are of considerable concern to UK society as almost 60% of UK deaths are directly attributed to these diseases. The impact of polyamides on diseases with aberrant gene expression could provide considerable benefits to patients and generally enhance the health and wellbeing of British society. * Nanotechnology (Timeframe 5-10 years) - This technology could also benefit industrial sectors with molecular electronics one long term possibility. With a cost effective polyamide method available there is potential to utilize polyamides in the bottom up construction of molecular electronic devices by facilitating the deposition of conductive, semi-conductive or insulating regions along DNA architectures. This development is the basis of a current EPSRC grant (EP/E055095/1). Communications and Engagement * Engagement with Beneficiaries - This follow on fund project will impact significantly on academic groups and industry who have an interest in preparing and using gene silencing technology. This would include life science groups investigating gene expression both in vitro and in vivo, peptide synthesis companies preparing gene silencing agents (such as peptide nucleic acids or PNA), as well as biotech and pharmaceutical companies looking to validate a biological target or small molecule drug candidates. * Research collaborations - We envisage that our polyamide technologywill enhance existing collaborations [Rant, Munich and Yu, Newcastle] in the molecular diagnostics field as well as facilitating new collaborations with groups interested in controlling gene expression in new biological systems. * Dissemination and Communication - Aspects of this research is expected to yield several high impact publications in periodicals such as Journal of the American Chemical Society, Angewandte Chemie and Organic Letters after protection of IP. Burley is also active in disseminating information to the wider public through the Burley group website [www.burleylabs.co.uk] as well as through the local (Leicester Mercury) and national (British Satellite News, the BBC, Daily Mail). * Training - This follow on fund will provide a postdoctoral research associate (PDRA) the opportunity to engage in an exciting and challenging translational project. The PDRA working will be expected to play an active role in the technical development of preparing polyamides suitable for testing by potential end users as well as liaising with interested parties in the technology either at Trade Fairs or through meetings and will engage in publication writing and the delivery of research presentations. It is envisaged that the training that the PDRA will receive will help develop a level of entrepreneurship within academic culture.